crossing96/oncoscreening huggingface dataset:
Role of a schistosoma haematobium specific microRNA as a predictive and prognostic tool for bilharzial bladder cancer in Egypt.	"Urinary bladder cancer is a common malignancy in Egypt, thus reliable methodologies are required for screening and early detection. In this study, we analyzed the gene expression of a Schistosoma hematobium specific microRNA ""Sha-miR-71a"" and mitogen-associated protein kinase-3 (MAPK-3) in the urine samples of 50 bladder cancer patients and 50 patients with benign bilharzial cystitis. Fifty control subjects were also tested. Indirect hemagglutination test (IHA) diagnosed 70% of studied cancer cases as bilharzial associated bladder cancer (BBC), while histopathological examination detected only 18%. Urinary Sha-miR-71a & MAPK-3 revealed enhanced expression in BBC (p-value = 0.001) compared to non-bilharzial bladder cancer (NBBC) cases. Patients with chronic bilharzial cystitis exhibited a significant increase in gene expression compared to those with acute infection (p-value = 0.001). Sha-miR-71a and MAPK-3 showed good sensitivity and specificity in the diagnosis of BBC when analyzed by the receiver operating characteristic (ROC) curve. They were also prognostic regarding malignancy grade. Both biomarkers showed a positive correlation. Our results revealed that IHA is a reliable test in the diagnosis of bilharziasis associated with bladder cancer, and that Sha-miR-71a and MAPK-3 provide non-invasive specific biomarkers to diagnose BBC, as well as a potential role in testing bilharzial patients for risk to develop cancer."	bladder
Acetylation of putative arylamine and alkylaniline carcinogens in immortalized human fibroblasts transfected with rapid and slow acetylator N-acetyltransferase 2 haplotypes.	Exposure to alkylanilines found in tobacco smoke and indoor air is associated with risk of bladder cancer. Genetic factors significantly influence the metabolism of arylamine carcinogens and the toxicological outcomes that result from exposure. We utilized nucleotide excision repair (NER)-deficient immortalized human fibroblasts to examine the effects of human N-acetyltransferase 1 (NAT1), CYP1A2, and common rapid (NAT2*4) and slow (NAT2*5B or NAT2*7B) acetylator human N-acetyltransferase 2 (NAT2) haplotypes on environmental arylamine and alkylaniline metabolism. We constructed SV40-transformed human fibroblast cells that stably express human NAT2 alleles (NAT2*4, NAT2*5B, or NAT2*7B) and human CYP1A2. Human NAT1 and NAT2 apparent kinetic constants were determined following recombinant expression of human NAT1 and NAT2 in yeast for the arylamines benzidine, 4-aminobiphenyl (ABP), and 2-aminofluorene (2-AF), and the alkylanilines 2,5-dimethylaniline (DMA), 3,4-DMA, 3,5-DMA, 2-6-DMA, and 3-ethylaniline (EA) compared with those of the prototype NAT1-selective substrate p-aminobenzoic acid and NAT2-selective substrate sulfamethazine. Benzidine, 3,4-DMA, and 2-AF were preferential human NAT1 substrates, while 3,5-DMA, 2,5-DMA, 3-EA, and ABP were preferential human NAT2 substrates. Neither recombinant human NAT1 or NAT2 catalyzed the N-acetylation of 2,6-DMA. Among the alkylanilines, N-acetylation of 3,5-DMA was substantially higher in human fibroblasts stably expressing NAT2*4 versus NAT2*5B and NAT2*7B. The results provide important insight into the role of the NAT2 acetylator polymorphism (in the presence of competing NAT1 and CYP1A2-catalyzed N-acetylation and N-hydroxylation) on the metabolism of putative alkyaniline carcinogens. The N-acetylation of two alkylanilines associated with urinary bladder cancer (3-EA and 3,5-DMA) was modified by NAT2 acetylator polymorphism.	bladder
Uncovering the expression patterns and the clinical significance of miR-182, miR-205, miR-27a and miR-369 in patients with urinary bladder cancer.	BACKGROUND: Given the high recurrence and progression rates and the absence of reliable markers for early detection and prognosis prediction of patients with urothelial bladder cancer (BCa), the exploration of new biomarkers with high specificity is imperative. Mainly, microRNAs (miRNAs), which are involved in the initiation and the progression of BCa. Herein, the expression patterns of miR-182, miR-205, miR-27a and miR-369 were evaluated in patients with urothelial BCa. METHODS AND RESULTS: The expression levels of the miRNAs were investigated in 90 FFPE tissue samples (23 LG NMIBC, 44 HG NMIBC, 23 MIBC) and 10 non tumoral bladder tissues using TaqMan based RT-qPCR. Data analysis was performed using 2(-ΔΔCT) method. Correlation to clinical characteristics of the patients was performed using descriptive statistics and the receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic value of all miRNAs. MiR-27a, miR-205 and miR-369 were down-regulated whereas miR-182 was up-regulated in patients compared to controls (p < 0.001). MiR-205 and miR-182 positively segregate between NMIBC and MIBC (p = 0.002 and p = 0.000 respectively) whereas the distribution of miR-27a's expression among these tumor groups was almost significant (p = 0.05) and that of miR-369's expression was irrelevant (p = 0.618). Interestingly, miR-182 was discriminative between LG NMIBC and HG NMIBC (p < 0.001) and Ta/T1 tumors (p = 0.000). Furthermore, high levels of miR-182 were potentially predictive of progression in NMIBC patients (p = 0.01). CONCLUSION: Collectively, a selection of miRNAs was found to be aberrantly expressed in BCa suggesting a potential diagnostic value in BCa. In addition, the clinical value of miR-182 and miR-205 as potential prognosis biomarkers was highlighted. Indeed, our data provide additional insights into cancer biology. Further functional or target studies are mandatory to strengthen these findings.	bladder
Mesenchymal stem cells-derived exosomal microRNA-139-5p restrains tumorigenesis in bladder cancer by targeting PRC1.	microRNAs (miRNAs) can be delivered to tumor cells where they exert their function via mesenchymal stem cells (MSCs)-derived exosomes. This study investigated exosomal transfer of miR-139-5p to bladder cancer cells and their role in the regulation of tumorigenesis. The dysregulation of polycomb repressor complex 1 (PRC1) in bladder cancer was characterized by RNA quantification, and its functional significance in bladder cancer cells was identified by loss-of-function experiments. We predicted the miR-139-5p that could play a role in regulating PRC1, which was further verified using dual-luciferase reporter gene assay. Next, we altered the expression of miR-139-5p and PRC1 in bladder cancer cells to identify their functions in cancer progression. Bladder cancer cells were co-cultured with exosomes isolated from human umbilical cord mesenchymal stem cells (hUCMSCs) over-expressing miR-139-5p. The intercellular transfer of miR-139-5p along with in vitro and in vivo functions was determined using gain- and loss-of-function approaches. Our results revealed that PRC1 levels were increased in bladder cancer tissues and cells, and silencing PRC1 appeared to impede the cell proliferation, migration, and invasion potentials. In addition, miR-139-5p was observed to be down-regulated in bladder cancer, which targeted PRC1 and reduced its expression, hereby resulting in ameliorated tumorigenic characteristics of bladder cancer cells in vitro. Furthermore, we noted that miR-139-5p from hUCMSCs-derived exosomes could be transferred into bladder cancer cells to down-regulate the PRC1 expression. Moreover, hUCMSCs-derived exosomal miR-139-5p conferred a suppressive role on bladder cancer development in vitro and in vivo. These data together supported the tumor-inhibiting role of MSCs-derived exosomal miR-139-5p in bladder cancer, highlighting a promising therapeutic strategy.	bladder
Preoperative Monocyte-to-lymphocyte Ratio Predicts for Intravesical Recurrence in Patients With Urothelial Carcinoma of the Upper Urinary Tract After Radical Nephroureterectomy Without a History of Bladder Cancer.	BACKGROUND: This study aimed to investigate the preoperative monocyte-to-lymphocyte ratio (MLR) as a biomarker for intravesical recurrence (IVR) in upper urinary tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU) for the first time. PATIENTS AND METHODS: This study involved the clinical data of 255 patients with UTUC without a history of bladder cancer who had undergone RNU from March 2004 to February 2019 at an academic institution. The associations between MLR and IVR were assessed with Kaplan-Meier method and Cox regression analysis. RESULTS: The median follow-up was 43.93 months. Of the 255 patients, 37 developed IVR during the follow-up period. Kaplan-Meier analysis revealed that patients with high MLR (> 0.22) had poor IVR-free survival (P = .001); this prognostic value was in accordance with patients with high grade and more advanced stage UTUC. Cox regression preoperative models showed that ureteral tumor site (hazard ratio [HR], 2.784; P = .005), surgical approach (HR, 2.745; P = .008), and high MLR (HR, 4.085; P < .001) were an independent risk factor for IVR. These factors were used as a signature to establish a prognostic risk model, which revealed significant differences among the 3 subgroups of patients with low, intermediate, and high risk (P < .001). CONCLUSION: Ureteral tumor site, surgical approach, and preoperative MLR are significant predictors for IVR in patients with UTUC after RNU. MLR may become a useful biomarker to predict IVR in patients with UTUC after RNU.	bladder
Centrosome Protein 78 Is Overexpressed in Muscle-Invasive Bladder Cancer and Is Associated with Tumor Molecular Subtypes and Mutation Signatures.	BACKGROUND Centrosome aberrations have long been linked to tumorigenesis. Centrosome protein 78 (CEP78) is a centrosome component that is required to regulate the cell cycle, but its role in bladder cancer has not been elucidated. MATERIAL AND METHODS Real-time quantitative polymerase chain reaction and immunohistochemistry were used to examine the expression of CEP78 in bladder cancer tissues and adjacent non-cancer tissues. RESULTS Analysis of the RNA-Seq data from the TCGA (The Cancer Genome Atlas) MIBC cohort (n=408) revealed that CEP78 was overexpressed in tumor tissues, which was confirmed with fresh-frozen and formalin-fixed paraffin-embedded specimens collected from 28 and 33 MIBC patients, respectively, in the present study. The clinicopathological relevance of CEP78 was further investigated. High CEP78 expression was found to be correlated with non-papillary histological type, luminal, basal-squamous and neuronal molecular subtypes, TP53 mutation, RB1 mutation, wild-type FGFR3, PPARG fusion and amplification, high total number of single-nucleotide variants, and high neoantigen load, but it was not associated with tumor stages or overall survival. CONCLUSIONS The results of this study suggest that CEP78 plays in a role in promoting the development of MIBC and could be a novel diagnostic and therapeutic target.	bladder
Automatic recognition of bladder tumours using deep learning technology and its clinical application.	BACKGROUND: Bladder cancer is a kind of tumors with a high recurrence rate. The improvement of the cure rate and prognosis of bladder tumor depends on the accurate recognition of bladder tumor under the cystoscope. AIMS: To verify that deep learning technology can identify bladder cancer images. MATERIALS AND METHODS: In this study, 1200 cystoscopic cancer images from 224 patients with bladder cancer and 1150 cystoscopic images from 221 patients with no bladder cancer were collected. Three convolutional neural networks (LeNet, AlexNet and GoogLeNet), and the EasyDL deep learning platform were used to train deep learning models to distinguish images of bladder cancer. The diagnostic efficiency of deep learning model and urology experts was compared. RESULTS: The efficiency of EasyDL was the highest, and the accuracy was 96.9%. The efficiency of GoogLeNet was the second highest, and the accuracy was 92.54%. Among the 33 bladder cancer nodes and 11 no bladder cancer nodes, the accuracy of the neural network was 83.36% and that of medical experts was 84.09% (p > 0.05). DISCUSSION: This study used convolutional neural networks to recognize bladder tumor in the clinical. Although these three networks (LeNet, AlexNet and GoogLeNet) had a relatively basic network architecture, they achieved good results in the classification task of cystoscopic images. The deep learning system had a recognition efficiency no less than that of experienced clinical experts. CONCLUSION: This study proved the validity of the convolutional neural network for bladder tumor diagnosis based on the cystoscope.	bladder
Bergenin inhibits bladder cancer progression via activating the PPARγ/PTEN/Akt signal pathway.	Bladder cancer is one of the most common malignant tumors in the urinary system with high mortality and morbidity. Evidence revealed that bergenin could affect the development of cancer. Here, we aimed to investigate the effect of bergenin on bladder cancer progression and its mechanism. The effect of bergenin on cell function was first detected, followed by assessing the changes of the epithelial-mesenchymal transition (EMT) in bergenin-treated cells. The effect of bergenin on peroxisome proliferator-activated receptor γ (PPARγ)/phosphatase and tensin homolog (PTEN)/Akt signal pathway was measured by Western blotting, followed by the rescue experiments. The results showed that bergenin treatment significantly decreased cell viability and increased G1 phase arrest, accompanied by reduced expression of Ki67, cycling D1, and cycling B1 in bladder cancer cells. Apoptosis was induced by bergenin in bladder cancer cells, as evidenced by increased Bax and cleaved caspase 3 protein levels and decreased Bcl-2 level in bergenin-treated cells. Meanwhile, the inhibition of the invasion, migration, and EMT was also observed in bergenin-treated cells. Mechanism studies showed that bergenin treatment could activate PPARγ/PTEN/Akt signal pathway, as evidence by the increased nucleus PPARγ and phosphatase and tensin homolog (PTEN) expression and decreased Akt expression. Moreover, PPARγ inhibitor administration inverted the effects of bergenin on bladder cancer cell function, including the proliferation, apoptosis, invasion, and migration in bladder cancer cells. Our findings revealed that bergenin could inhibit bladder cancer progression via activating the PPARγ/PTEN/Akt signal pathway, indicating that bergenin may be a potential therapeutic medicine for bladder cancer treatment.	bladder
Open-label, Multicenter, Phase II Study of RC48-ADC, a HER2-Targeting Antibody-Drug Conjugate, in Patients with Locally Advanced or Metastatic Urothelial Carcinoma.	PURPOSE: To evaluate the efficacy and safety of RC48-ADC, a novel humanized anti-HER2 antibody conjugated with monomethyl auristatin E, in patients with HER2(+) locally advanced or metastatic urothelial carcinoma (mUC) refractory to standard therapies. PATIENTS AND METHODS: This was a phase II, open-label, multicenter, single-arm study of patients with HER2(+) (IHC status 3+ or 2+) locally advanced or mUC who previously failed at least one line of systemic chemotherapy. The primary endpoint was the objective response rate (ORR) assessed by a blinded independent review committee (BIRC). The secondary endpoint included progression-free survival (PFS), disease control rate, duration of response, overall survival (OS), and safety. RESULTS: Forty-three patients were enrolled. The median follow-up was 20.3 months. The overall confirmed ORR as assessed by the BIRC was 51.2% [95% confidence interval (CI), 35.5%-66.7%]. Similar responses were observed in prespecified subgroups, such as those with liver metastasis and those previously treated with anti-programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) therapies. The median PFS and OS were 6.9 months (95% CI, 5.6-8.9) and 13.9 months (95% CI, 9.1-NE), respectively. The most common treatment-related adverse events (TRAE) were hypoesthesia (60.5%), alopecia (55.8%), and leukopenia (55.8%). Twenty-five (58%) patients experienced grade 3 TRAEs, including hypoesthesia (23.3%) and neutropenia (14.0%). No grade 4 or grade 5 TRAEs occurred. CONCLUSIONS: RC48-ADC demonstrated a promising efficacy with a manageable safety profile in patients with HER2(+) locally advanced or mUC who had failed at least one line of systemic chemotherapy.	bladder
Oral Recombinant Methioninase Sensitizes a Bladder Cancer Orthotopic Xenograft Mouse Model to Low-dose Cisplatinum and Prevents Metastasis.	BACKGROUND/AIM: The aim of the study was to determine if oral recombinant methioninase (o-rMETase) can sensitize an orthotopic bladder tumor in nude mice to low-dose cisplatinum (CDDP). MATERIALS AND METHODS: The green fluorescent protein (GFP)-expressing UM-UC-3-GFP bladder cancer was surgically orthotopically implanted (SOI) to the bladder in nude mice. The treatment was initiated when the primary tumor volume reached 100 mm(3) Mice were assigned to 3 groups: G1: Saline vehicle (0.1 ml per mouse, oral, twice per day); G2: low-dose CDDP (0.5 mg/kg, intraperitoneal twice per week); G3: o-rMETase + low-dose CDDP (100 units per mouse, oral, twice per day + 0.5 mg/kg, intraperitoneal twice per week, respectively). Tumor volume and body weight were measured twice per week. The expression of Ki-67 was detected by immunohistochemistry to evaluate cell proliferation. RESULTS: The combination of o-rMETase and low-dose CDDP increased inhibition efficacy compared to low-dose CDDP monotherapy, on primary-tumor growth (p=0.032) and metastasis (p=0.002). CONCLUSION: The combination of o-rMETase with low-dose CDDP has future clinical potential for bladder cancer.	bladder
Recurrent bladder cancer in aging societies: Importance of major histocompatibility complex class I antigen presentation.	Aging is associated with an insufficient immune response that may lead to the initiation and progression of various malignancies. Bladder cancer (BC), prevalent in elderly patients, predominantly presents as recurrent nonmuscle invasive BC that requires further treatment. There is much interest in the activation of patients' immune cells with the focus on CD8+ T cells. Successful therapy should also ensure the efficient presentation of BC antigens by major histocompatibility complex (MHC) class I molecules. The purpose of this systematic review is to present the existing literature on the role of MHC class I in BC research and therapy. The bibliographic databases PubMed and Web of Science were searched for articles published between January 2009 and September 2020 that addressed MHC class I relationship to BC. We searched for available relevant publications on MHC class I and its role and regulation in BC, aging and MHC class I importance in BC immunotherapy. Based on the provided evidence, we propose that the loss of MHC class I expression in BC may lead to its recurrence after the transurethral resection and unresponsiveness to Bacillus Calmette-Guerin immunotherapy. We discuss different ways to enhance MHC class I antigen presentation to CD8+ T cells in BC treatment. The immune status characterized by MHC class I expression patterns and cancer-infiltrating immune cells may provide valuable prognostic information about which patients may benefit from transurethral resection of BC and additional immunotherapy.	bladder
Small Nucleolar RNAs (snoRNAs)-Based Risk Score Classifier Predicts Overall Survival in Bladder Carcinoma.	"BACKGROUND Bladder carcinoma (BLCA) is a leading cause of cancer-related deaths worldwide. The aim of this work was to develop an accurate stratification in predicting the prognosis and directing the treatment of BLCA patients based on small nucleolar RNAs (snoRNAs). MATERIAL AND METHODS Expression profiles of snoRNAs were downloaded from the SNORic database. The expression profiles and clinical outcomes of BLCA patients were analyzed. Survival-associated snoRNAs were identified and used to develop a novel risk score classifier. Genes in the whole genome that were significantly correlated with the included prognostic snoRNAs were used for functional enrichment analysis. RESULTS The results showed that age, American Joint Committee on Cancer (AJCC) stage, and tumor status were significantly correlated with overall survival (OS) of BLCA patients. We selected 12 survival-associated snoRNAs to build a prognostic signature. Patients were separated into high- and low-risk groups based on the median value of the risk score. Patients in the high-risk group and low-risk group have distinct clinical outcomes. The AJCC TNM stage showed moderate utility as a prognostic indicator for clinical outcome prediction. Then, clinical parameters and risk scores were entered in multivariate Cox analysis. Notably, the prognostic signature remained an independent significant prognostic risk factor. The pathway analysis suggested that these genes were enriched in several types of cancer and ""Focal adhesion"" pathways. CONCLUSIONS The prognostic signature defined by expression profiles of 12 survival-associated snoRNAs appears to be an excellent predictor of the clinical outcome of BLCA patients."	bladder
Alterations of DNA damage response genes correlate with response and overall survival in anti-PD-1/PD-L1-treated advanced urothelial cancer.	DNA damage response (DDR) gene alterations in cancer are associated with a higher tumor mutational burden (TMB) and may impact clinical outcomes of urothelial cancer (UC). Here, we explore the prognostic role of DDR alterations in advanced UC treated with anti-PD-1/PD-L1 agents. The study included 53 patients who had FoundationOne genomic sequencing and received anti-PD-1/PD-L1 therapy. Fisher exact test and trend test were used to assess differences in objective response rate (ORR). Overall survival (OS) was measured from the time of initial UC diagnosis and Cox proportional hazard regression analysis was performed to calculate hazard ratio (HR) and 95% confidence interval (CI). The cohort had a median age of 66 with 64% receiving platinum-based chemotherapy. DDR alterations (including ATM) were associated with a non-significantly higher ORR to PD-1/PD-L1 blockade (41% vs. 21%, p = 0.136). Patients with DDR alterations (excluding ATM) had non-significantly longer OS, likely due to a small sample size (HR = 0.53, 95% CI 0.20-1.38, p = 0.19). ATM alterations were associated with a non-significantly higher ORR (40% vs. 29%, p = 0.6), but also with significantly shorter OS (HR = 5.7, 95% CI 1.65-19.74, p = 0.006). Patients with ≥ 3 DDR alterations (including ATM) had substantially higher TMB (p = 0.01) and higher ORR (80%) with PD-1/PD-L1 blockade versus 24% ORR in patients with <3 DDR alterations. In summary, DDR alterations were associated with non-significantly higher ORR and longer OS for patients with advanced UC receiving anti-PD-1/PD-L1 agents. ATM alterations were associated with shorter OS.	bladder
An 18-gene signature based on glucose metabolism and DNA methylation improves prognostic prediction for urinary bladder cancer.	BACKGROUND: Glucose metabolism and DNA methylation play important roles in cancers. We aimed to identify glucose metabolism-related genes that were DNA methylation associated to establish a prognostic signature of bladder cancer (BLCA). METHODS: With BLCA sample transcriptome data from The Cancer Genome Atlas (TCGA) and methylation data from TCGA 450 K microarray, glucose metabolism-related genes associated to prognosis and DNA methylation were identified and a prognostic signature was established. GSEA and WGCNA analysis were performed and two genes, UCHL1 and PYCR1, were selected for functional validations. RESULTS: 18 target genes were identified and the signature based on them was considered an effective and independent prognostic factor. Several pathways were enriched in the high-risk group by GSEA and three modules of genes were identified by WGCNA. UCHL1 and PYCR1 proliferated proliferation, migration and invasion ability of bladder cancer cells. CONCLUSIONS: The 18-gene signature is an independent prognostic factor for bladder cancer patients.	bladder